新型喹唑啉酮衍生物的设计合成与抗植物病原真菌活性研究

Design,Synthesis and Antifungal Activities of Novel Quinazolinone Derivatives

为寻找新型高效的绿色杀菌剂先导化合物,以喹唑啉酮为药效母核,通过活性药效团拼合,设计合成了19个新颖的1-芳酰基-2-芳基-3-乙基喹唑啉-4(^(1)H)-酮衍生物7.目标分子经^(1)H NMR、^(13)C NMR和HRMS进行确认,并评价了其抗植物病原真菌活性.初步离体抑菌活性显示,在50 mg/L浓度下,目标化合物对6种受试真菌均具有较良好的抑制效果.其中,7a对小麦赤霉病菌和玉米纹枯病菌的EC_(50)分别为12.727和12.413 mg/L,优于阳性对照百菌清(14.323和13.339 mg/L).分子表面静电势研究显示,7a中酰胺键周围的静电势为负值,易与受体中带正电的氨基酸残基产生作用.以上结果为新型喹唑啉酮类杀菌剂先导的开发提供了新的研究思路.

Plant pathogenic fungi have caused enormous yield and economic losses in agricultural production.In order to discover effective antifungal agents,a series of 19 novel quinazolinone derivatives 7 were designed and synthesized based on molecular splicing approach.The classical pharmacophore of amide was introduced into N-1 of quinazolinone skeleton.The structures were confirmed by ^(1)H NMR,^(13)C NMR and HRMS.Preliminary in vitro antifungal test showed that the target compounds exhibited moderate to favourable activities against six kind of plant pathogenic fungi at the concentration of 50 mg/L.Compound 7 a had significant inhibitory effects on Fusarium graminearum and Rhizoctonia solani with EC_(50) of 12.727 and 12.413 mg/L,respectively,which were better than chlorothalonil(14.323 and 13.339 mg/L).Molecular electrostatic potential of 7 a indicated that the amide moieties located in the negative potential region and might generate hydrogen bond with target amino acid residue.The above results provided an effective strategy for the development of quinazolinone antifungal agents.